Prospective Study on the Synergistic Effect of Tauroursodeoxycholic Acid Combined With Immunotherapy in Hepatocellular Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Overall Survival (OS)
研究概览
简要总结
This is a clinical trial that aims to evaluate whether adding a bile acid called tauroursodeoxycholic acid (TUDCA) can improve the effects of immunotherapy in patients with advanced liver cancer (hepatocellular carcinoma).
Immunotherapy has shown promise in treating this type of cancer, but not all patients respond well. TUDCA is known to help protect liver cells and may improve the liver's immune environment, potentially making immunotherapy more effective.
In this study, 300 patients with advanced liver cancer will be randomly assigned to receive either immunotherapy alone or immunotherapy combined with TUDCA.
Researchers will look at how well the cancer responds, whether the treatment helps more patients become eligible for surgery, and how safe the combination is.
The goal is to find a more effective and better tolerated treatment for patients with liver cancer.
详细描述
This prospective, randomized, controlled clinical trial investigates the efficacy and safety of combining tauroursodeoxycholic acid (TUDCA) with immune checkpoint inhibitors (ICIs) in patients with advanced hepatocellular carcinoma (HCC).
Immunotherapy using PD-1 or PD-L1 inhibitors has become a cornerstone in treating advanced HCC. However, a significant proportion of patients exhibit limited response or develop resistance. One contributing factor may be the immunosuppressive liver tumor microenvironment, which impairs T cell activation and infiltration. TUDCA is a hydrophilic bile acid that exhibits cytoprotective and anti-inflammatory effects, and may enhance the immune response by improving liver immune homeostasis.
In this study, 300 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC will be enrolled and randomly assigned to receive either PD-1/PD-L1 inhibitor monotherapy or combination therapy with TUDCA. The treatment cycle will last for 6 months, with a follow-up period of at least 6 months after treatment completion.
The primary outcome is objective response rate (ORR) as measured by RECIST 1.1 and mRECIST criteria. Secondary endpoints include progression-free survival (PFS), overall survival (OS), conversion to surgical eligibility, and biomarker dynamics.
Safety and tolerability will be closely monitored throughout the study. Dose-limiting toxicities, adverse events, and liver function parameters will be assessed regularly. The trial will also explore immune and inflammatory biomarkers associated with response to treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed diagnosis of primary hepatocellular carcinoma (HCC).
- •Unresectable advanced HCC classified as Barcelona Clinic Liver Cancer (BCLC) stage C.
- •Age ≥ 18 years.
- •No prior systemic anti-tumor therapy for HCC before first dose of study treatment.
- •At least one measurable lesion according to RECIST v1.1, or a measurable lesion with clear progression after local treatment based on RECIST v1.
- •Adequate organ and bone marrow function within 7 days prior to enrollment, with no blood products, growth factors, albumin, or other intravenous/subcutaneous corrective treatment within 14 days prior to laboratory assessment:
- •Hematology:
- •Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count (PLT) ≥ 75 × 10⁹/L Hemoglobin (Hb) ≥ 9.0 g/dL
- •Liver function:
- •Total bilirubin (TBil) ≤ 2 × ULN ALT and AST ≤ 5 × ULN Serum albumin ≥ 28 g/L
- •Alkaline phosphatase (ALP) ≤ 5 × ULN
- •Renal function:
- •Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance (CCr) ≥ 50 mL/min (calculated by Cockcroft-Gault formula) Urinalysis shows urine protein < 2+; if urine protein ≥ 2+, 24-hour urine collection must show protein < 1g/24h
- •Coagulation:
- •International Normalized Ratio (INR) ≤ 2.3 or prothrombin time (PT) prolongation ≤ 6 seconds
- •Estimated life expectancy of ≥ 12 weeks.
排除标准
- •History of hepatic encephalopathy or liver transplantation.
- •Acute cholecystitis, acute cholangitis, patients with frequent biliary colic attacks, complete biliary obstruction, or gallbladder dysfunction (inability to contract and empty).
- •Patients with Child-Pugh class C or decompensated cirrhosis, including those with a history of severe hepatic encephalopathy or refractory ascites due to liver disease.
- •Patients with a previous diagnosis of biliary atresia without adequate biliary drainage (e.g., failed biliary-enteric anastomosis).
- •Pregnant or breastfeeding women.
研究组 & 干预措施
TUDCA + ICI
Participants will receive a combination of tauroursodeoxycholic acid (TUDCA) and an immune checkpoint inhibitor.
干预措施: TUDCA (Tauroursodeoxycholic Acid) Supplementation (Drug)
TUDCA + ICI
Participants will receive a combination of tauroursodeoxycholic acid (TUDCA) and an immune checkpoint inhibitor.
干预措施: Immune checkpoint inhibitor (ICI) (Drug)
ICI Monotherapy
Participants will receive standard immune checkpoint inhibitor monotherapy.
干预措施: Immune checkpoint inhibitor (ICI) (Drug)
结局指标
主要结局
Overall Survival (OS)
时间窗: Up to 12 months
Time from randomization to death from any cause.
Progression-Free Survival (PFS)
时间窗: Up to 12 months
Time from randomization to disease progression or death from any cause, assessed by RECIST 1.1 criteria.
次要结局
- Disease Control Rate (DCR)(up to 12 months)
- Change in Renal Function Indicators(From baseline to 12 weeks (every 4-6 weeks))
- Change in Hematologic Parameters(From baseline to 12 weeks (every 4-6 weeks))
- Change in Immune Inflammatory Markers(From baseline to 12 weeks (every 4-6 weeks))
- Change in Serum Bile Acid Levels(From baseline to 12 weeks (every 4-6 weeks))